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Chemical Structure| 576-83-0 Chemical Structure| 576-83-0

Structure of 576-83-0

Chemical Structure| 576-83-0

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Product Citations

Product Citations

Zhou, Tongliang ; Gao, Pengcheng ; Bisz, Elwira ; Dziuk, Błażej ; Lalancette, Roger ; Szostak, Roman , et al.

Abstract: We describe the development of [(NHC)Pd(cinnamyl)Cl] complexes of ImPy (ImPy = imidazo[1,5-a]pyridin-3-ylidene) as a versatile class of precatalysts for cross-coupling reactions. These precatalysts feature fast activation to monoligated Pd(0) with 1:1 Pd to ligand ratio in a rigid imidazo[1,5-a]pyridin-3-ylidene template. Steric matching of the C5-substituent and N2-wingtip in the catalytic pocket of the catalyst framework led to the discovery of ImPyMesDipp as a highly reactive imidazo[1,5-a]pyridin-3-ylidene ligand for Pd-catalyzed cross-coupling of nitroarenes by challenging C–NO2 activation. Kinetic studies demonstrate fast activation and high reactivity of this class of well-defined ImPy–Pd catalysts. Structural studies provide full characteristics of this new class of imidazo[1,5-a]pyridin-3-ylidene ligands. Computational studies establish electronic properties of sterically-restricted imidazo[1,5-a]pyridin-3-ylidene ligands. Finally, a scalable synthesis of C5-substituted imidazo[1,5-a]pyridin-3-ylidene ligands through Ni-catalyzed Kumada cross-coupling is disclosed. The method obviates chromatographic purification at any of the steps, resulting in a facile and modular access to ImPy ligands. We anticipate that well-defined [Pd–ImPy] complexes will find broad utility in organic synthesis and catalysis for activation of unreactive bonds.

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Alternative Products

Product Details of [ 576-83-0 ]

CAS No. :576-83-0
Formula : C9H11Br
M.W : 199.09
SMILES Code : CC1=C(Br)C(C)=CC(C)=C1
MDL No. :MFCD00000073
InChI Key :RRTLQRYOJOSPEA-UHFFFAOYSA-N
Pubchem ID :68473

Safety of [ 576-83-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 576-83-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 49.04
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.63
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.71
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.37
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.98
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.52

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.86
Solubility 0.0278 mg/ml ; 0.000139 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.4
Solubility 0.0791 mg/ml ; 0.000397 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.42
Solubility 0.00766 mg/ml ; 0.0000385 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

Yes
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-4.88 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<2.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.15

Application In Synthesis of [ 576-83-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 576-83-0 ]

[ 576-83-0 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 576-83-0 ]
  • [ 326-64-7 ]
  • (5-chloro-2-trifluoromethoxy-phenyl)-(2,4,6-trimethyl-phenyl)-amine [ No CAS ]
  • 2
  • [ 1455-20-5 ]
  • [ 576-83-0 ]
  • [ 1044231-46-0 ]
  • 3
  • [ 121-43-7 ]
  • [ 576-83-0 ]
  • [ 34907-53-4 ]
YieldReaction ConditionsOperation in experiment
Synthesis of bis(4-bromophenyl)(mesityl)borane To a stirred solution of 2-bromo-1,3,5-trimethylbenzene (5.9 g, 30.0 mmol) in dry Et2O (100 mL) is added dropwise n-butyllithium (1.60 M in hexane, 18.75 mL, 30.0 mmol) at -78 C. After stirring for 1 h, the mixture is added trimethyl borate (6.2 g, 60.0 mmol) and is stirred overnight at room temperature. The solvent of mixture is evaporated, and the residue is distilled under reduced pressure (200 torr) to afford clear liquid dimethyl mesitylboronate intermediate. To the solution of dimethyl mesitylboronate (1 g, 5.21 mmol) in dry THF (20 mL) is added (4-bromophenyl)magnesium bromide (0.5 M in THF, 32 mL, 16 mmol) at -78 C. under nitrogen atmosphere. The reaction mixture is allowed to stir at room temperature and poured into a large amount of water, and extracted with chloroform. The combined organic layer is washed with water, and dried over anhydrous Na2SO4. The residue is purified by column chromatography on silica gel (eluent: hexane/CHCl3=8:1, v/v) to afford a white solid (8.4 g, 63%).
  • 4
  • [ 620-08-6 ]
  • [ 576-83-0 ]
  • [ 594-19-4 ]
  • [ 33513-42-7 ]
  • [ 82257-15-6 ]
YieldReaction ConditionsOperation in experiment
61% TERT-BUTYLLITHIUM (90.6 mL, 154 mmol; 1.7 M in pentane) was added via cannula to a stirred solution of tetrahydrofuran (380 mL) under an atmosphere of nitrogen at room temperature. The reaction mixture was cooled to-78C before adding 2-bromomesitylene (11.3 mL, 74.1 mmol) dropwise. The reaction mixture was allowed to stir for 1 hour at- 78C. To the reaction mixture at-78C was added 4-methoxypyridine (5.79 ML, 57 mmol) dropwise, and the resulting mixture was stirred AT-23C for 3 hours. The reaction mixture was then re-cooled to-78C and DIMETHYLFORMAMIDE (6.62 mL, 85.5 mmol) was added and stirring was continued for 1 hour AT-78C. The reaction mixture was quenched slowly AT-78C with saturated aqueous sodium chloride solution (100 mL) and allowed to warm to room temperature slowly. To the reaction mixture was added diethyl ether (200 mL) and the layers were separated. The aqueous layer was extracted with diethyl ether (2 x 150 mL) and the combined organic layers were dried over potassium carbonate (20 g). The potassium carbonate was removed by filtration and washed with diethyl ether (100 mL) and the solvent removed under reduced pressure. The resulting crude 4-methoxy-3- pyridinecarboxaldehyde was purified by column chromatography (SiO2, 5: 95 ethanol: ethyl acetate) to give 4.79 g of the title intermediate as a yellow solid (61% yield; >98% purity by'H NMR). Analytical Data : HNMR (300 MHz, CDCL) 8 10.43 (s, 1H, CHO), 8.87 (s, 1H, ArH), 8.63 (d, 1H, J= 6, ARH), 6.92 (d, 1H, J= 6, ART), 3.98 (s, 3H, CH30).
  • 6
  • [ 80041-89-0 ]
  • [ 576-83-0 ]
  • [ 4810-04-2 ]
  • [ 108-67-8 ]
 

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Technical Information

Categories

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